The major objective of the proposed research is to study the chemical and physical properties of several selenium functional groups believed to be present at the active site of the mammalism selenoenzyme glutathione peroxidase (GSH-Px; GSH-H2O2 oxidoreductase, EC 1.11.1.9). The focus of the work will be the chemistry of selenenic acids, whose instability and high reactivity have made chemical studies very difficult. A number of important reactions of organoselenium compounds (selenoxide syn elimination (2,3)sigmatropic rearrangements of selenoxides, and electrophilic additions of RSeX to olefins) are though to have selenenic acids or their derivatives as reactive intermediates. We will use the selenoxide syn elimination to prepare selenenic acids at temperatures low enough so that they can be observed spectroscopically and their chemistry studied. The systems chosen will include several that are models for the selenocysteine active site of GSH-Px. Mechanistic studies will be carried out on the reactions of some of these selenenic acids with hydroperoxides and thiols (a probable metabolic role and known in vitro reaction of GSH-Px) to determine if the catalytic activity of the enzyme can be achieved in carefully designed model systems. It is hoped that these experiments will provide the framework for a better understanding of the redox processes catalyzed by GSH-Px. Spectroscopic properties of a variety of organoselenium compounds will be measured to provide stereochemical and conformational information and aid in the identification of unknown selenium species. Selenium-77 chemical shifts and coupling constants between selenium and other nuclei (H,13C) will be determined. Finally, the preparation and reactions of alkyl selenons will be studied.